The specific aim of the research proposal presented herein is to study how lymphocytes derived from the thymus (T cells) respond per se to a variety of experimental maneuvers that have been shown to affect the immune response. The response of the T cells will be assayed by measuring their DNA synthesis. Different sub-populations of T cells will be studied. These include, thymic, splenic, lymph node, and peritoneal exudate cells and sub-populations of these cells. Cells will be fractionated by sensitivity to cortisone, cytoxan, vinblastine, levamisole, and ALS and different fractions will be recombined. The response to antigen will be measured in the spleens and lymph nodes of lethally irradiated recipients. We will study the acquisition of immunological memory by transferring T cells which have localized and responded in the spleens and lymph nodes of primary hosts to secondary hosts. We will separate short term from long term memory by varying the time of stimulation with antigen in the secondary hosts. We will test the effects of various drugs, antigen-antibody complexes and multiple injections of antigens on the acquisition of memory. We will use our memory acquisition assay to test the significance of the DNA synthetic response to genetically determined antigens other than those determined by the major histocompatibility locus ("LD" locus, "M" locus, "Y antigen"). We will do cell fractionation studies (discontinuous BSA gradients) to see if responding cells can be separated from suppressor cells. When suppressor populations are identified, we will look to see if they have differential susceptibility to drug treatment. We will also look to see if drug treatment can abolish the acquisition of specific immunological unresponsiveness (tolerance) in some situations. We also plan to examine the cellular basis for the immuno-suppressive effects produced by non-specific T cell activators.